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1.
Medicine (Baltimore) ; 99(41): e22647, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031325

RESUMO

RATIONALE: Signet ring cell carcinoma of the stomach is prone to relapse and metastasis after traditional surgical treatment, and the prognosis is also poor. We improved the concept of treatment and conducted cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) combined with intraperitoneal (IP) and intravenous (IV) chemotherapy for a gastric signet-cell carcinoma patient. PATIENT CONCERNS: A 65-year-old male patient with complaint of intermittent hematemesis for over 10 days was referred to our hospital for treatment. The patient developed hematemesis of 800 mL without obvious causes on May 27, 2015, accompanied by dizziness and amaurosis fugax. After the bleeding was stopped with medicinal treatment, diagnostic gastroscopy revealed an ulcer at the less curvature of the stomach, with biopsy pathology diagnosis as severe atypical hyperplasia, which was confirmed to be poorly differentiated adenocarcinoma by a second biopsy. In past medical history, the patient had 5 coronary stents implanted because of coronary atherosclerotic heart disease 3 years ago. DIAGNOSIS: Gastric cancer (cT4NxMx) according to the patient's history and biopsy pathology. INTERVENTIONS: the patient was treated surgery-based multidisciplinary treatments integrating CRS + HIPEC and IP + IV adjuvant chemotherapy. The CRS was curative distal gastrectomy with D2 lymphadenectomy, and HIPEC was cisplatin 120 mg plus mitomycin C 30 mg at 43 °C, for 60 minutes. Final pathological diagnosis of after surgery was: poorly differentiate adenocarcinoma with signet-ring cells, with invasion beyond the serosal layer and into the duodenum, 10/23 lymph nodes positive, nerve invasion, vascular tumor thrombi, Borrmann type IV, Lauren type diffuse. TNM stage was pT4aN3M0, IIIC. After operation, the patient received 6 courses of IV chemotherapy with oxaliplatin and 5-fluorouracil/Tegafur Gimeracil Oteracil Potassium capsules, and IP chemotherapy with docetaxel and carboplatin. OUTCOMES: Regular follow-up till July 20, 2020, revealed that the patient has a disease-free survival of over 61+ months. LESSONS: CRS + HIPEC combined with IP + IV chemotherapy achieved long-term disease-free survival for this patient with gastric signet-ring cell carcinoma and deserve further study. This new treatment modality deserves appropriate consideration in routine clinical practice for patients with advanced gastric cancer.


Assuntos
Antineoplásicos/administração & dosagem , Carcinoma de Células em Anel de Sinete/cirurgia , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Neoplasias Gástricas/cirurgia , Idoso , Carcinoma de Células em Anel de Sinete/tratamento farmacológico , Terapia Combinada , Humanos , Masculino , Neoplasias Gástricas/tratamento farmacológico
2.
Life Sci ; 259: 118395, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32905830

RESUMO

In recent years, natural products have increasingly attracted more attention because of their potential anticancer activity and low intrinsic toxicity. Hispidulin is a natural flavonoid with a wide range of biological activities, including anti-inflammatory, antifungal, antiplatelet, anticonvulsant, anti-osteoporotic, and notably anticancer activities. Numerous in vivo and in vitro studies have shown that hispidulin, as a potential anticancer drug, affects cell proliferation, apoptosis, cell cycle, angiogenesis, and metastasis. Moreover, hispidulin exhibits synergistic anti-tumor effects when combined with some common clinical anticancer drugs (e.g., gemcitabine, 5-fluoroucil, sunitinib, temozolomide, and TRAIL). The combination of hispidulin and chemotherapeutic drugs reduces the efflux of chemotherapeutic drugs, enhances the chemosensitivity of cancer cells, and reverses drug resistance. Herein, we outlined the anticancer effects of hispidulin in various cancers and its intracellular molecular targets and related mechanisms of its anticancer activity. Based on the available literature, it can be established that hispidulin has significant potential to become an important complementary medicine for cancer prevention and treatment. However, more in-depth in vitro and in vivo studies should be conducted to support its translation from bench to bedside.


Assuntos
Antineoplásicos/uso terapêutico , Flavonas/uso terapêutico , Flavonoides/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico
3.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(4): 426-434, 2020 Apr 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32879068

RESUMO

For resectable gastric cancer, although radical surgery is still the main treatment, methods of operation and the curative effect of operation are still in the stage of exploration for metastatic gastric cancer. Radiotherapy, chemotherapy and molecular targeted therapy also play an important role in prolonging the survival period of patients with gastric cancer. Postoperative radiotherapy and chemotherapy can prolong the survival time, but for patients with locally advanced gastric cancer, the preoperative radiotherapy and chemotherapy can also further improve the survival period of patients compared with direct operation. In addition, with the development and using of molecular targeted drugs, such as antiangiogenic agents, immunosuppressive drugs and so on, the survival period of patients with gastric cancer has been further extended.


Assuntos
Neoplasias Esplênicas , Neoplasias Gástricas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Gastrectomia , Humanos , Terapia Neoadjuvante
4.
Yonsei Med J ; 61(9): 750-761, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32882759

RESUMO

PURPOSE: Gastric cancer (GC) is a malignant tumor with a high mortality rate. Drug resistance is a major obstacle to GC therapy. This study aimed to investigate the role and mechanism of exosomal circPRRX1 in doxorubicin resistance in GC. MATERIALS AND METHODS: HGC-27 and AGS cells were exposed to different doses of doxorubicin to construct doxorubicin-resistant cell lines. Levels of circPRRX1, miR-3064-5p, and nonreceptor tyrosine phosphatase 14 (PTPN14) were detected by quantitative real-time PCR or Western blot assay. Then, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, transwell, and Western blot assays were used to explore the function of circPRRX1 in GC cells. Interactions among circPRRX1, miR-3064-5p, and PTPN14 were confirmed by dual-luciferase reporter assay. The in vivo function of circPRRX1 was analyzed in a xenograft tumor model. RESULTS: CircPRRX1 was highly expressed in doxorubicin-resistant GC cell lines. Knockdown of circPRRX1 reversed doxorubicin resistance in doxorubicin-resistant GC cells. Additionally, extracellular circPRRX1 was carried by exosomes to spread doxorubicin resistance. CircPRRX1 silencing reduced doxorubicin resistance by targeting miR-3064-5p or regulating PTPN14. In GC patients, high levels of circPRRX1 in serum exosomes were associated with poor responses to doxorubicin treatment. Moreover, depletion of circPRRX1 reduced doxorubicin resistance in vivo. CONCLUSION: CircPRRX1 strengthened doxorubicin resistance by modulating miR-3064-5p/PTPN14 signaling and might be a therapeutic target for GC patients.


Assuntos
Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/genética , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Linhagem Celular Tumoral , Exossomos/genética , Exossomos/metabolismo , Exossomos/patologia , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio , Humanos , MicroRNAs/metabolismo , Proteínas Tirosina Fosfatases não Receptoras/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
5.
Anticancer Res ; 40(10): 5815-5821, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988910

RESUMO

BACKGROUND/AIM: Glioma-associated oncogene 1 (GLI1) is an important transcription factor in the hedgehog signalling pathway and tumour formation. We evaluated the clinical significance of GLI1 expression as a prognostic factor in patients with locally advanced gastric cancer (GC). PATIENTS AND METHODS: GLI1 expression levels were measured by quantitative real-time polymerase chain reaction analysis of cancerous and adjacent normal mucosa specimens obtained from 142 patients with Stage II/III GC administered adjuvant chemotherapy with S-1 after curative resection. The associations of GLI1 expression with clinicopathological features and survival were evaluated. RESULTS: Clinicopathological features and GLI1 expression showed no association. Overall survival was significantly poorer in the high compared to the low GLI1 expression group (p=0.04). Multivariate analysis revealed that GLI1 expression was a significant independent prognostic factor [p=0.019, hazard ratio (HR)=1.94, 95% confidence interval (CI)=1.70-3.38]. CONCLUSION: GLI1 expression may be a useful prognostic marker in patients with locally advanced GC.


Assuntos
Biomarcadores Tumorais/genética , Prognóstico , Neoplasias Gástricas/tratamento farmacológico , Proteína GLI1 em Dedos de Zinco/genética , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Combinação de Medicamentos , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Estadiamento de Neoplasias , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Tegafur/administração & dosagem , Tegafur/efeitos adversos
6.
Anticancer Res ; 40(10): 5393-5397, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988858

RESUMO

BACKGROUND/AIM: We established a new patient-derived orthotopic xenograft (PDOX) model of gastric cancer liver metastasis and evaluated the efficacy of a novel combination chemotherapy, gemcitabine (GEM) plus 5-fluorouracil (5-FU), compared to a standard regimen of oxaliplatinum (L-OHP) plus 5-FU on the liver metastasis. MATERIALS AND METHODS: Patient-derived gastric cancer was established in nude mice from the patient' s surgical tumor specimen. A single tumor fragment was implanted in the liver of nude mice. The mice with tumors were treated by GEM plus 5-FU or L-OHP plus 5-FU. RESULTS: GEM plus 5-FU or L-OHP plus 5-FU significantly and similarly inhibited tumor growth on the liver compared to the untreated control (p=0.007, p=0.02, respectively). CONCLUSION: GEM plus 5-FU could be a novel future clinical alternative to L-OHP plus 5-FU in gastric cancer patients who cannot tolerate platinum drugs.


Assuntos
Desoxicitidina/análogos & derivados , Fluoruracila/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Desoxicitidina/farmacologia , Modelos Animais de Doenças , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Oxaliplatina/farmacologia , Estômago/efeitos dos fármacos , Estômago/patologia , Neoplasias Gástricas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Medicine (Baltimore) ; 99(34): e21807, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846818

RESUMO

BACKGROUND: Huaier granules, the aqueous product of Huaier (Trametes robiniophila Murr.) extract, are a broad-spectrum anti-tumor drug and have been widely used for the treatment of gastric cancer (GC). The aim of this study is to systematically investigate the efficacy and safety of Huaier granules combined with chemotherapy in the treatment of GC. METHODS: Three English databases and four Chinese databases will be searched from its inception to July 2020. Two methodological trained researchers will select the qualified studies for data extraction independently. Cochrane Risk of Bias tool will be used to assess the risk of bias of included studies. The RevMan 5.2 and stata 14.0 software will be applied for statistical analyses. Statistical heterogeneity will be computed by Cochrane X and I tests. Sensitivity analysis will be conducted to evaluate the stability of the results. The publication bias will be evaluated by funnel plots and Egger's test. The quality of evidence will be assessed by the GRADE system. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: The conclusion of our systematic review will provide evidence to judge whether Huaier granules combined with chemotherapy is an effective intervention for patient with GC. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/9BVJD.


Assuntos
Misturas Complexas/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Misturas Complexas/efeitos adversos , Humanos , Metanálise como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Trametes
8.
PLoS One ; 15(7): e0235848, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32735623

RESUMO

BACKGROUND: Second-line treatments boost overall survival in advanced gastric cancer (AGC). However, there is a paucity of information as to patterns of use and the results achieved in actual clinical practice. MATERIALS AND METHODS: The study population comprised patients with AGC in the AGAMENON registry who had received second-line. The objective was to describe the pattern of second-line therapies administered, progression-free survival following second-line (PFS-2), and post-progression survival since first-line (PPS). RESULTS: 2311 cases with 2066 progression events since first-line (89.3%) were recorded; 245 (10.6%) patients died during first-line treatment and 1326/2066 (64.1%) received a second-line. Median PFS-2 and PPS were 3.1 (95% CI, 2.9-3.3) and 5.8 months (5.5-6.3), respectively. The most widely used strategies were monoCT (56.9%), polyCT (15.0%), ramucirumab+CT (12.6%), platinum-reintroduction (8.3%), trastuzumab+CT (6.1%), and ramucirumab (1.1%). PFS-2/PPS medians gradually increased in monoCT, 2.6/5.1 months; polyCT 3.4/6.3 months; ramucirumab+CT, 4.1/6.5 months; platinum-reintroduction, 4.2/6.7 months, and for the HER2+ subgroup in particular, trastuzumab+CT, 5.2/11.7 months. Correlation between PFS since first-line and OS was moderate in the series as a whole (Kendall's τ = 0.613), lower in those subjects who received second-line (Kendall's τ = 0.539), especially with ramucirumab+CT (Kendall's τ = 0.413). CONCLUSION: This analysis reveals the diversity in second-line treatment for AGC, highlighting the effectiveness of paclitaxel-ramucirumab and, for a selected subgroup of patients, platinum reintroduction; both strategies endorsed by recent clinical guidelines.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sistema de Registros/estatística & dados numéricos , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Uso de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Compostos de Platina/administração & dosagem , Compostos de Platina/uso terapêutico , Neoplasias Gástricas/patologia , Análise de Sobrevida
9.
Medicine (Baltimore) ; 99(32): e21619, 2020 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-32769923

RESUMO

BACKGROUND: Kanglaite injection is a broad-spectrum anti-tumor drug, which is extracted from the seeds of the Chinese medicinal herb Coix lacryma-jobi, and has been widely used for the treatment of gastric cancer (GC). This study aimed to systematically investigate the efficacy and safety of Kanglaite injection for the treatment of GC. METHODS: We will perform the comprehensive literature search in English and Chinese electronic database from its inception to June 2020. Two trained researchers will independently select the qualified studies for data extraction and assess the quality and risk of bias. Cochrane Risk of Bias tool will be used to assess the risk of bias of included studies. The outcomes included overall response rate, complete response rate, 3-year progression-free survival rate, 3-year overall survival rate, and different types of treatment-related adverse events. Funnel plot analysis and Egger test will be used to assess the publication bias. Finally, the quality of evidence will be assessed by the grading of recommendations assessment, development, and evaluate system . We will calculate the risk ratio as well as their 95% confidence intervals of these outcomes and pool the results using RevMan 5.4 software and STATA 16.0 software. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: The conclusion of our systematic review will provide evidence to judge whether Kanglaite injection is an effective intervention for patient with GC. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/HF679.


Assuntos
Protocolos Clínicos , Medicamentos de Ervas Chinesas/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Medicamentos de Ervas Chinesas/normas , Humanos , Metanálise como Assunto , Neoplasias Gástricas/fisiopatologia , Revisões Sistemáticas como Assunto , Resultado do Tratamento
10.
Int J Nanomedicine ; 15: 5073-5082, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764937

RESUMO

Objective: To prepare xanthatin (XA)-loaded polydopamine (PDA) nanoparticles (PDA-XA-NPs) and to investigate their adhesion and bioavailability. Materials and methods: PDA-XA-NPs were synthesized and characterized using transmission electron microscopy, zeta potential analysis and encapsulation efficiency analysis. Their in vitro release kinetics and inhibitory effects on gastric cancer were studied. The adhesion of PDA-XA-NPs was evaluated by in vivo imaging atlas. The pharmacokinetics of PDA-XA-NPs and XA was compared. Results: PDA-XA-NPs had a spherical shape, a particle size of about 380 nm, an encapsulation efficiency of (82.1 ± 0.02) % and a drug loading capacity of (5.5 ± 0.1)%. The release of PDA-XA-NPs in PBS was stable and slow, without being affected by pH. The adhesion capacity of PDA-XA-NPs for mucin was significantly higher than that of bulk drug. The gastric mucosal retention of PDA-XA-NPs reached 89.1% which significantly exceeded that of XA. In vivo imaging showed that PDA-XA-NPs targeting the stomach were retained for a period of time. The pharmacokinetics study showed that PDA-XA-NPs had a longer retention time and a slower drug release than those of XA. In vitro experiments confirmed that PDA-XA-NPs exerted similar inhibitory effects on gastric cancer to those of XA, which lasted for a period of time. Conclusion: High-adhesion NPs were constructed. Gastric cancer was targeted by orally administered PDA-XA-NPs, as a potentially feasible therapy. Eventually, the bioavailability of XA was increased.


Assuntos
Antineoplásicos Fitogênicos/farmacocinética , Furanos/farmacocinética , Nanopartículas/química , Neoplasias Gástricas/tratamento farmacológico , Animais , Antineoplásicos Fitogênicos/química , Disponibilidade Biológica , Linhagem Celular Tumoral , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Furanos/química , Mucosa Gástrica/efeitos dos fármacos , Humanos , Concentração de Íons de Hidrogênio , Indóis/química , Masculino , Camundongos Endogâmicos ICR , Microscopia Eletrônica de Transmissão , Nanopartículas/metabolismo , Tamanho da Partícula , Polímeros/química , Ratos Sprague-Dawley , Neoplasias Gástricas/patologia
11.
Medicine (Baltimore) ; 99(28): e20727, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664067

RESUMO

RATIONALE: Most gastric cancer patients are diagnosed at mid- to late-stage and lose the chance of radical surgery, medical treatment is especially important to prolong the survival of patients. Apatinib mesylate, which is a small molecule vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor, could be used as antiangiogenesis therapy for gastric cancer. PATIENT CONCERNS: A 67-year-old man sought medical care for upper abdominal discomfort. DIAGNOSIS: The patient was diagnosed as mixed medullary differentiated gastric adenocarcinoma, and immunohistochemistry suggested HER-2 (2+). INTERVENTIONS: The patient received chemotherapy consisting of oxaliplatin combined with S-1 as first-line treatment, and targeted therapy with apatinib mesylate as second-line treatment. OUTCOMES: After 4 months of first-line chemotherapy, the patient received apatinib treatment immediately at a dose of 500 mg/d orally and died of cardiac arrest with 8.5 months of overall survival. During this period of targeted therapy with apatinib mesylate, this male patient suffered mammary gland development besides other common adverse reactions. LESSONS: This case report is the first to report the case of male mammary gland development after oral apatinib.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma Medular/tratamento farmacológico , Glândulas Mamárias Humanas/efeitos dos fármacos , Piridinas/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Idoso , Humanos , Masculino
12.
Zhonghua Wei Chang Wai Ke Za Zhi ; 23(7): 657-660, 2020 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-32683826

RESUMO

The standard treatment for advanced gastric cancer remains surgery-based comprehensive treatment. The D2 radical surgery has made outstanding contributions to the standarlization of gastric cancer surgery, which has improved patients' prognosis and quality of life. In recent years, neoadjuvant chemotherapy has achieved a certain effect on the treatment of advanced gastric cancer. With the continuous development of the concept of membrane anatomy in gastric cancer surgery, new surgical challenges have also been raised. For patients after neoadjuvant therapy, there is heated controversy in the possibility of completing radical gastrectomy with membrane anatomical concept for gastric cancer. We believe that if neoadjuvant therapy pushes mesenteric cancer cell back into the mesentery, theoretically membrane anatomy combined with neoadjuvant therapy is beneficial to the treatment efficacy of advanced gastric cancer. However, membrane anatomy has two important problems when combined with neoadjuvant therapy: (1) After neoadjuvant chemotherapy, there are varying degrees of edema around the stomach tissue, which will affect the visualization of anatomic planes. In addition, because the patients' coagulation function is damaged to a certain extent, it is difficult to avoid bleeding or minimize bleeding during the operation. Therefore, it is still controversial whether the patients with gastric cancer after neoadjuvant chemotherapy can undergo radical gastrectomy with membrane anatomy. (2) For patients with complete pathological remission, whether to obtain the maximum rate of pathological remission through intensive neoadjuvant therapy, or to obtain the survival benefit of patients with membrane anatomy surgery in clinic is still controversial. Faced with these confusions, multi-center clinical researches on the application of membrane anatomy surgery after neoadjuvant therapy is the only solution.


Assuntos
Gastrectomia/métodos , Mesentério/cirurgia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Edema/etiologia , Gastrectomia/efeitos adversos , Humanos , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/métodos , Mesentério/anatomia & histologia , Mesentério/irrigação sanguínea , Mesentério/patologia , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Prognóstico , Qualidade de Vida , Neoplasias Gástricas/patologia
13.
Life Sci ; 257: 118100, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32679149

RESUMO

AIM: Nexrutine, an herbal extract of Phellodendron amurense, has been found to play a tumor-suppressive role in many cancers. However, its role in the pathogenesis of gastric cancer remains unclear. MATERIALS AND METHODS: Gastric cancer cells (SGC-7901 and MGC-803) were treated with nexrutine, and cell proliferation, invasion and apoptosis were analyzed. And the MGC-803 cells-derived xenograft mouse models were fed pelleted diet containing 600 mg/kg nexrutine for 21 days after inoculation. Mechanically, we focused on the influences of nexrutine on the levels and activation of STAT3 and NF-κB as well as their upstream regulator FAK. Additionally, we further verified whether nexrutine affected the proliferation, invasion and apoptosis of gastric cancer cells via FAK by upregulating FAK expression before nexrutine treatment. KEY FINDINGS: We found nexrutine inhibited the viability, invasion, and expression levels of PCNA, CyclinD1 and Bcl-2, promoted the apoptosis and Bax expression, decreased levels of STAT3, phospho-STAT3, NF-κB p65, phospho-p65, FAK and phospho-FAK in gastric cancer cells. Overexpression of FAK reversed the impacts of nexrutine on the levels of STAT3, phospho-STAT3, NF-κB p65, phospho-p65, as well as the malignant characteristics of gastric cancer cells. Moreover, nexrutine suppressed tumor volumes and weights, and decreased expression and phosphorylation of FAK, STAT3 and NF-κB p65 in vivo. SIGNIFICANCE: Nexrutine inhibited the malignant progression of gastric cancer via negatively regulating STAT3/NF-κB signaling pathway by suppressing FAK expression and activation.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Quinase 1 de Adesão Focal/genética , Extratos Vegetais/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Progressão da Doença , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , NF-kappa B/metabolismo , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
14.
Gene ; 757: 144937, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32640300

RESUMO

MicroRNAs (miRNAs) are a group of non-coding RNAs that have critical roles in regulation of expression of genes. They can inhibit or decrease expression of target genes mostly via interaction with 3' untranslated region of their targets. Their crucial roles in the regulation of expression of tumor suppressor genes and oncogenes have potentiated them as contributors in tumorigenesis. Moreover, their stability in body fluids has enhanced their potential as cancer biomarkers. In the present review article, we describe the role of miRNAs in the pathogenesis of gastric cancer and advances in application of miRNAs as biomarkers and therapeutic targets in this kind of malignancy.


Assuntos
Biomarcadores Tumorais/genética , MicroRNAs/genética , Neoplasias Gástricas/genética , Animais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Humanos , MicroRNAs/sangue , MicroRNAs/metabolismo , Transdução de Sinais , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo
15.
Lancet Oncol ; 21(8): 1066-1076, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32653053

RESUMO

BACKGROUND: Margetuximab, a novel, investigational, Fc-engineered, anti-HER2 monoclonal antibody, is designed to more effectively potentiate innate immunity than trastuzumab. We aimed to evaluate the safety, tolerability, and antitumour activity of margetuximab plus pembrolizumab (an anti-PD-1 monoclonal antibody) in previously treated patients with HER2-positive gastro-oesophageal adenocarcinoma. METHODS: CP-MGAH22-05 was a single-arm, open-label, phase 1b-2 dose-escalation and cohort expansion study done at 11 academic centres in the USA and Canada and 15 centres in southeast Asia (Korea, Taiwan, and Singapore) that enrolled men and women aged 18 years or older with histologically proven, unresectable, locally advanced or metastatic, HER2-positive, PD-L1-unselected gastro-oesophageal adenocarcinoma, with an Eastern Cooperative Oncology Group performance status of 0 or 1, who had progressed after at least one previous line of therapy with trastuzumab plus chemotherapy in the locally advanced unresectable or metastatic setting. In the dose-escalation phase, nine patients were treated: three received margetuximab 10 mg/kg intravenously plus pembrolizumab 200 mg intravenously every 3 weeks and six received the recommended phase 2 dose of margetuximab 15 mg/kg plus pembrolizumab 200 mg intravenously every 3 weeks. An additional 86 patients were enrolled in the phase 2 cohort expansion and received the recommended phase 2 dose. The primary endpoints were safety and tolerability, assessed in the safety population (patients who received at least one dose of either margetuximab or pembrolizumab) and the objective response rate as assessed by the investigator according to both Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, in the response-evaluable population (patients with measurable disease at baseline and who received the recommended phase 2 dose of margetuximab and pembrolizumab). This trial is registered with ClinicalTrials.gov, NCT02689284. Recruitment for the trial has completed and follow-up is ongoing. FINDINGS: Between Feb 11, 2016, and Oct 2, 2018, 95 patients were enrolled. Median follow-up was 19·9 months (IQR 10·7-23·1). The combination therapy showed acceptable safety and tolerability; there were no dose-limiting toxicities in the dose-escalation phase. The most common grade 3-4 treatment-related adverse events were anaemia (four [4%]) and infusion-related reactions (three [3%]). Serious treatment-related adverse events were reported in nine (9%) patients. No treatment-related deaths were reported. Objective responses were observed in 17 (18·48%; 95% CI 11·15-27·93) of 92 evaluable patients. INTERPRETATION: These findings serve as proof of concept of synergistic antitumour activity with the combination of an Fc-optimised anti-HER2 agent (margetuximab) along with anti-PD-1 checkpoint blockade (pembrolizumab). FUNDING: MacroGenics.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Receptor ErbB-2/antagonistas & inibidores , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
16.
Lancet Oncol ; 21(8): 1045-1056, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32682457

RESUMO

BACKGROUND: S-1 plus leucovorin and oxaliplatin showed promising efficacy for treatment of advanced gastric cancer in a randomised phase 2 study. We aimed to evaluate the efficacy and safety of oral TAS-118 (S-1 plus leucovorin) and oxaliplatin versus S-1 plus cisplatin in patients with advanced gastric cancer. METHODS: We did a randomised, open-label, phase 3 trial in 62 centres across Japan and South Korea. Patients aged 20 years or older, with a histologically confirmed advanced gastric cancer with negative or unknown HER2 status, with Eastern Cooperative Oncology Group performance status of 0 or 1, measurable or evaluable metastatic lesions, and no previous treatment were randomly assigned (1:1) via an interactive web response system using the minimisation method, stratified by performance status, presence of a measurable lesion, and country, to receive TAS-118 (S-1 40-60 mg and leucovorin 25 mg orally twice daily for 7 days) plus oxaliplatin (85 mg/m2 intravenously on day 1) every 2 weeks, or S-1 (40-60 mg orally twice daily) for 21 days plus cisplatin (60 mg/m2 intravenously on day 1 or 8) every 5 weeks. The primary endpoint was overall survival in patients who had advanced gastric cancer with measurable or evaluable metastatic lesions and who received the study drug. Safety was assessed in all patients who received the study drug. This study was registered at ClinicalTrials.gov, NCT02322593. FINDINGS: Between Jan 28, 2015, and Dec 5, 2016, 711 patients were randomised to TAS-118 plus oxaliplatin (n=356) or S-1 plus cisplatin (n=355). 11 untreated patients and 19 ineligible patients were excluded from the primary analysis (TAS-118 plus oxaliplatin group n=347, S-1 plus cisplatin group n=334) following recommendation from the independent data monitoring committee. After median follow-up of 26·0 months (IQR 22·0-32·8), median overall survival was 16·0 months (95% CI 13·8-18·3) in the TAS-118 plus oxaliplatin group and 15·1 months (95% CI 13·6-16·4) in the S-1 plus cisplatin group (hazard ratio 0·83, 95% CI 0·69-0·99; p=0·039). The most common grade 3 or higher adverse events in the 352 patients in the TAS-118 plus oxaliplatin group and the 348 patients in the S-1 plus cisplatin group were anaemia (56 [16%] vs 64 [18%]), neutropenia (54 [15%] vs 88 [25%]), decreased appetite (53 [15%] vs 46 [13%]), diarrhoea (33 [9%] vs 15 [4%]), and peripheral sensory neuropathy (30 [9%] vs one [<1%]). Serious adverse events were observed in 155 (44%) of 352 patients in the TAS-118 plus oxaliplatin group and 159 (46%) of 348 patients in the S-1 plus cisplatin group. Two treatment-related deaths occurred in the TAS-118 plus oxaliplatin group (pulmonary tuberculosis and viral pneumonia). INTERPRETATION: TAS-118 plus oxaliplatin showed a clinically meaningful improvement in efficacy compared with S-1 plus cisplatin, and could be considered a new first-line treatment option for advanced gastric cancer in Asian patients. FUNDING: Taiho Pharmaceutical and Yakult Honsha.


Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Oxaliplatina/administração & dosagem , Oxaliplatina/efeitos adversos , Ácido Oxônico/administração & dosagem , Ácido Oxônico/efeitos adversos , Tegafur/administração & dosagem , Tegafur/efeitos adversos
17.
Anticancer Res ; 40(8): 4271-4279, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727754

RESUMO

BACKGROUND/AIM: Skeletal muscle mass (SMM) is often depleted in patients with gastric cancer undergoing gastrectomy. Using a novel method, we evaluated the effect of SMM depletion after gastrectomy on disease prognosis. PATIENTS AND METHODS: The maximum cross-sectional area of the psoas-muscle (MCA-PM) was measured before surgery and at 1 year after in 233 patients with gastric cancer who underwent radical gastrectomy to determine the ratio (MCA-PMR) as an indicator of SMM depletion. RESULTS: The MCA-PMR cutoff value was set at 90%, and patients were divided into the groups with <90% and ≥90%. MCA-PMR <90% was an independent prognostic factor for all patients. In 88 patients who received adjuvant chemotherapy including S-1, the 5-year cancer-specific survival rate was significantly better for those with MCA-PMR ≥90% than for those with MCA-PMR <90% (84.1% vs. 59.1%; p=0.010; hazard ratio=2.974; 95% confidence interval=1.241-7.124). CONCLUSION: SMM depletion after gastrectomy can be measured using the MCA-PMR. This novel measurement can be easily implemented in the clinical setting.


Assuntos
Gastrectomia/efeitos adversos , Músculo Esquelético/patologia , Sarcopenia/etiologia , Neoplasias Gástricas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Sarcopenia/patologia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Taxa de Sobrevida , Adulto Jovem
18.
Zhonghua Wai Ke Za Zhi ; 58(8): 614-618, 2020 Aug 01.
Artigo em Chinês | MEDLINE | ID: mdl-32727193

RESUMO

Objective: To compare the accuracy of abdominal enhanced CT and endoscopic ultrasound in the staging of gastric cancer after neoadjuvant chemotherapy (yc stage). Methods: Clinic data of 86 locally advanced gastric cancer patients admitted in Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute from April 2015 to November 2017 were analyzed retrospectively. Totally 86 patients completed both abdominal enhanced CT and endoscopic ultrasound after neoadjuvant chemotherapy. There were 60 males and 26 females, aged (57.8±9.7) years (range: 32 to 76 years). The diagnostic accuracy of abdominal enhanced CT and endoscopic ultrasound for yc stage were calculated by the area under the multiclass receiver operation characteristic curve (M-AUC), retrospectively. McNemar test was used to compared the diagnostic sensitivity. Results: The M-AUC of ycT stage evaluated by abdominal enhanced CT (CT-ycT stage) and by endoscopic ultrasound (EUS-ycT stage) was 0.614 and 0.704, respectively. For middle and lower gastric cancer, the M-AUC of CT-ycT stage was 0.599 and 0.613, respectively, while EUS-ycT stage was 0.558 and 0.709, respectively. For tumor in the lesser and non-lesser curvature, the M-AUC of CT-ycT stage was 0.630 and 0.607, respectively, while EUS-ycT stage was 0.616 and 0.749, respectively. For patients in CT-ycT1-CT-ycT4, there was no statistically significant difference in the sensitivity between CT-ycT stage and EUS-ycT stage (2/18, 2/15, 52.8%(19/36), 8/13 vs. 0, 4/15, 55.6%(20/36), 7/13; χ(2)=2.00, P=0.157; χ(2)=2.00, P=0.157; χ(2)=0.08, P=0.782; χ(2)=0.33, P=0.564). The M-AUC of ycN stage evaluated by abdominal enhanced CT (CT-ycN stage) was 0.654, while ycN stage evaluated by endoscopic ultrasound (EUS-ycN stage) was 0.533. For patients in CT-ycN0, there was statistically significant difference in the sensitivity between CT-ycN stage and EUS-ycN stage (12.7%(7/55) vs. 5.5%(3/55); χ(2)=4.00, P=0.046). For patients in CT-ycN1, N2, and N3, there was no statistically significant difference in the sensitivity between CT-ycN stage and EUS-ycN stage (2/19, 1/10, 0 vs. 1/19, 1/10, 0; χ(2)=1.00, P=0.317; the other P cannot be estimated). Conclusions: There was no significant difference between the diagnostic efficacy of abdominal enhanced CT and endoscopic ultrasound for yc stage of gastric cancer. Considering the invasiveness of ultrasound gastroscopy, it should not be recommend for patients after neoadjuvant chemotherapy routinely.


Assuntos
Antineoplásicos/administração & dosagem , Endossonografia , Estadiamento de Neoplasias/métodos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Tomografia Computadorizada por Raios X , Adulto , Idoso , Endossonografia/métodos , Endossonografia/normas , Feminino , Gastroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias/normas , Reprodutibilidade dos Testes , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Tomografia Computadorizada por Raios X/métodos , Tomografia Computadorizada por Raios X/normas
19.
Life Sci ; 257: 118051, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32634426

RESUMO

AIMS: Chemotherapy is an effective therapeutic modality which is commonly used for battling various cancers. However, several side effects induced by chemotherapeutic drugs would limit their clinical use. The present systematic review aims to evaluate the role of curcumin/curcuminoids co-administration during gastric cancer chemotherapy. METHODS: This systematic review was done according to PRISMA guidelines and a full systematic search in the electronic databases up to May 2020 using search terms in the titles and abstracts for the identification of relevant literature. 279 articles were found in electronic databases and 175 articles screened by title and abstract. Finally, 13 articles were included in this systematic review according to our inclusion and exclusion criteria. KEY FINDINGS: The findings indicated that gastric cancer chemotherapy induces cytotoxicity effects in various ways including a decrease of cell viability, colony formation, metastasis, tumor growth, and weight, as well as elevation of apoptosis pathway, oxidative stress pathway compared to the control group. Co-administration of curcumin/curcuminoids with chemotherapy synergistically increased the effects of anti-cancer chemotherapy compared to the group solo treated with chemotherapeutic agents. Also, in chemoresistance gastric cancer cells, co-administration of curcumin reduced chemoresistance mainly through the reduction of NF-κB activation and elevation of apoptosis. SIGNIFICANCE: According to the findings, the use of curcumin/curcuminoids during gastric cancer chemotherapy has chemosensitizing effects, and also it can reduce chemoresistance in gastric cancer.


Assuntos
Curcumina/uso terapêutico , Diarileptanoides/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Curcumina/metabolismo , Curcumina/farmacologia , Diarileptanoides/metabolismo , Diarileptanoides/farmacologia , Tratamento Farmacológico/métodos , Humanos
20.
Drugs Today (Barc) ; 56(7): 469-482, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32648857

RESUMO

Gastric cancer is one of the most common malignant tumors in the world. In China, its morbidity and mortality are second only to lung cancer. Chemotherapy combined with targeted therapy brings survival benefits to patients with advanced gastric cancer. Targets for targeted therapy of gastric cancer include human epidermal growth factor receptor (EGFR), human epidermal growth factor receptor 2 (HER2), vascular endothelial growth factor (VEGF), mammalian target of rapamycin (mTOR) and Claudin 18.2 (CLDN 18.2). The main challenge of tumor molecule-targeted drugs is resistance. The main mechanisms of drug resistance include tumor establishment of compensatory signaling pathways, target protein changes, tumor microenvironment changes, tumor heterogeneity and tumor adaptation to targeted drugs. The combined action of multiple drug resistance mechanisms promotes the development of targeted drug resistance. In order to attract the attention of researchers, this paper reviews the mechanisms of drug resistance in gastric cancer-targeted therapy. In addition, the research status of drug resistance in molecule-targeted therapy of gastric cancer is summarized. It is of great clinical significance to explore the drug resistance mechanisms of targeted drugs and reverse drug resistance in gastric cancer. Last, the future development of molecule-targeted therapy is prospected.


Assuntos
Antineoplásicos , Terapia de Alvo Molecular , Neoplasias Gástricas , Antineoplásicos/uso terapêutico , Sistemas de Liberação de Medicamentos , Resistência a Medicamentos , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/genética , Microambiente Tumoral , Fator A de Crescimento do Endotélio Vascular
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